Hyperpolarized MRI for Brain Tumor

Overseen By Wendy Ma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Susan Chang

Disqualifiers: Congestive heart failure, Myocardial infarction, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: Varies based on standard treatment protocols

140 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the treatment Hyperpolarized Carbon C 13 Pyruvate for brain tumors?

Research shows that hyperpolarized Carbon C 13 Pyruvate can help detect treatment responses in brain tumors by tracking changes in tumor metabolism, which is useful for early identification of treatment effectiveness. This method has been effective in other cancers, like breast cancer, by providing detailed metabolic information that can guide treatment decisions. ^{1 2 3 4 5}

Is hyperpolarized MRI using carbon-13 pyruvate safe for humans?

Research indicates that hyperpolarized carbon-13 pyruvate MRI has been safely used in humans, including healthy volunteers and pediatric patients with brain tumors, without reported adverse effects. ^{1 2 6 7 8}

How does the treatment Hyperpolarized MRI for Brain Tumor differ from other treatments for this condition?

Hyperpolarized MRI for brain tumors is unique because it uses a special form of MRI with hyperpolarized carbon-13 pyruvate to visualize and measure the metabolism of brain tumors in real-time. This method provides detailed metabolic information that can help assess tumor activity and response to treatment, which is not possible with standard imaging techniques. ^{1 2 4 9 10}

What is the purpose of this trial?

This pilot trial studies the side effects of hyperpolarized carbon C 13 pyruvate magnetic resonance imaging (MRI) in diagnosing participants with glioma. Diagnostic procedures, such as hyperpolarized carbon C 13 pyruvate MRI, may help find and diagnose glioma.

Research Team

Susan Chang, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for adults over 18 with a life expectancy of more than 12 weeks and diagnosed with glioma, who are not HIV-positive, pregnant or breastfeeding. Participants must have adequate kidney function, no severe heart failure or recent heart attacks, and no other cancers except certain skin cancers or cervical carcinoma in-situ unless in remission for at least 3 years.

Inclusion Criteria

I am over 18 years old and expected to live more than 12 weeks.

Patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must sign an authorization for the release of their protected health information.

I don't have any severe illnesses that would interfere with the study's imaging tests.

Exclusion Criteria

Subjects must be excluded from participating in this study if they are not able to comply with study and/or follow-up procedures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging and Injection

Participants receive one or two hyperpolarized carbon C 13 pyruvate injections intravenously and undergo MRI

1 day

1 visit (in-person)

Treatment

Participants in Cohort II receive standard radiation and temozolomide treatment outside of this study

Varies based on standard treatment protocols

Post-Treatment Imaging

Participants in Cohort II undergo MRI 4 weeks after completion of cancer therapy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 24 months

Treatment Details

Interventions

• Hyperpolarized Carbon C 13 Pyruvate
• Magnetic Resonance Imaging

Trial Overview The trial tests the safety of using hyperpolarized carbon C 13 pyruvate MRI to diagnose gliomas. It involves patients already scheduled for standard treatment with radiation and temozolomide (Cohort 2), as well as those with evaluable disease based on prior MR scans (Cohort 1).

Participant Groups

Group I: Cohort II (Hyperpolarized C13, MRI) Experimental Treatment 4 Interventions

Participants receive hyperpolarized carbon C 13 pyruvate IV and undergo MRI before treatment and 4 weeks after completion of cancer therapy given outside of this study.

Group II: Cohort I (Hyperpolarized C13, MRI) Experimental Treatment 2 Interventions

Participants receive hyperpolarized carbon C 13 pyruvate intravenously IV and undergo MRI. The second hyperpolarized 13 C injection/imaging will be started approximately 15 to 60 minutes after the first injection for those who are willing to receive two 13 C injections

Who Is Running the Clinical Trial?

Susan Chang

Lead Sponsor

Trials

5

Recruited

520+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Hyperpolarized [1-(13)C]pyruvate can effectively detect treatment responses in glioma tumors, which is challenging with traditional imaging methods like PET due to interference from normal brain tissue signals.

In a rat model, significant lactate labeling was observed in glioma tumors after treatment, with a notable decrease in the ratio of tumor lactate to blood pyruvate signal following whole brain irradiation, indicating a potential response to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detecting response of rat C6 glioma tumors to radiotherapy using hyperpolarized [1- 13C]pyruvate and 13C magnetic resonance spectroscopic imaging. Day, SE., Kettunen, MI., Cherukuri, MK., et al.[2021]

This study is the first to use hyperpolarized 13C MRI to visualize and measure how the human brain processes [2-13C]pyruvate, providing insights into cerebral energy metabolism.

In a trial involving 5 healthy volunteers, the technique allowed for the simultaneous assessment of glycolytic and oxidative metabolism by quantifying the conversion rates of pyruvate to lactate and glutamate, highlighting its potential for advanced metabolic imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized [2-13C]pyruvate MR molecular imaging with whole brain coverage. Chung, BT., Kim, Y., Gordon, JW., et al.[2023]

In a study involving three patients with glioblastoma, 13C MR spectroscopic imaging using hyperpolarized pyruvate successfully detected increased lactate production in tumor regions prior to surgical resection, indicating altered metabolism in these aggressive tumors.

The imaging technique correlated well with histological findings, confirming the presence of WHO grade IV glioblastoma and suggesting that this method could help identify metabolic changes associated with tumor aggressiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative imaging of glioblastoma patients using hyperpolarized 13C pyruvate: Potential role in clinical decision making. Chen, J., Patel, TR., Pinho, MC., et al.[2022]

Hyperpolarized 13C-MRI, which enhances the detection of tumor metabolism by 4-5 orders of magnitude, can track the metabolism of hyperpolarized [1-13C]pyruvate in cancer patients, providing insights into tumor activity and response to treatment.

Combining HP 13C-MRI with traditional 1H-MRI allows for detailed anatomical imaging and functional tumor analysis, potentially enabling early identification of patients who are not responding to therapies, although cost and technical challenges need to be addressed for broader clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized Carbon-13 MRI in Breast Cancer. Woitek, R., Brindle, KM.[2023]

Hyperpolarized carbon 13 MRI (13C MRI) is a groundbreaking imaging technique that allows for real-time, noninvasive observation of tissue metabolism, particularly useful in cancer research.

This method has shown promise in clinical applications such as tumor grading, tailoring treatment based on metabolic profiles, and detecting early treatment responses by monitoring metabolic changes before structural alterations in tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized Carbon 13 MRI: Clinical Applications and Future Directions in Oncology. Deen, SS., Rooney, C., Shinozaki, A., et al.[2023]

The study demonstrated that hyperpolarized carbon-13 (HP-13C) metabolic imaging is safe and well-tolerated in pediatric patients with brain tumors, with no adverse events reported during the imaging process.

HP-13C imaging successfully showed the brain's metabolism of HP [1-13C]pyruvate, indicating its potential as a useful tool for assessing metabolic changes in pediatric CNS tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Study of Hyperpolarized 13C Metabolic Imaging in Pediatric Patients with Diffuse Intrinsic Pontine Glioma and Other CNS Cancers. Autry, AW., Park, I., Kline, C., et al.[2022]

A stable hyperpolarized solution of [1-(13)C]-ethyl pyruvate was successfully developed, allowing for its use in metabolic imaging studies.

In a study involving anesthetized rats, hyperpolarized [1-(13)C]-ethyl pyruvate was compared to [1-(13)C]-pyruvate, demonstrating its potential for effective uptake and metabolic imaging in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic imaging in the anesthetized rat brain using hyperpolarized [1-13C] pyruvate and [1-13C] ethyl pyruvate. Hurd, RE., Yen, YF., Mayer, D., et al.[2021]

The study introduces a new method called Signal Amplification By Reversible Exchange (SABRE) that allows for the rapid production of hyperpolarized pyruvate for MRI, achieving results in just 6 minutes, making it a faster and more accessible option for metabolic imaging.

The produced hyperpolarized pyruvate solution is sterile, non-toxic, and pH neutral, indicating its safety for use in living organisms, which enhances its potential for diagnosing and monitoring cancer and other diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vivo Metabolic Imaging of [1-13 C]Pyruvate-d3 Hyperpolarized By Reversible Exchange With Parahydrogen. de Maissin, H., Groß, PR., Mohiuddin, O., et al.[2023]

Hyperpolarized MRI using [1-13C] pyruvate can effectively characterize energy metabolism in the human brain and identify altered cancer metabolism in brain tumors, as evidenced by the production of HP lactate from HP pyruvate.

This method shows promise as a quantitative metabolic biomarker for assessing tumor response, correlating well with standard clinical imaging techniques like MRI and PET/CT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic Imaging of the Human Brain with Hyperpolarized 13C Pyruvate Demonstrates 13C Lactate Production in Brain Tumor Patients. Miloushev, VZ., Granlund, KL., Boltyanskiy, R., et al.[2019]

In a study involving seven treatment-naive patients with glioblastoma, hyperpolarized 13C MRI revealed that the bicarbonate-to-pyruvate ratio was significantly lower in tumors compared to normal brain tissue, indicating altered metabolism in glioblastoma.

The study found strong correlations between tumor lactate and bicarbonate signal intensities with pyruvate signal intensity, suggesting that hyperpolarized 13C MRI can effectively monitor metabolic changes in glioblastoma, which may aid in understanding tumor behavior and treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging Glioblastoma Metabolism by Using Hyperpolarized [1-13C]Pyruvate Demonstrates Heterogeneity in Lactate Labeling: A Proof of Principle Study. Zaccagna, F., McLean, MA., Grist, JT., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Detecting response of rat C6 glioma tumors to radiotherapy using hyperpolarized [1- 13C]pyruvate and 13C magnetic resonance spectroscopic imaging. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Hyperpolarized [2-13C]pyruvate MR molecular imaging with whole brain coverage. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Preoperative imaging of glioblastoma patients using hyperpolarized 13C pyruvate: Potential role in clinical decision making. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Hyperpolarized Carbon-13 MRI in Breast Cancer. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Hyperpolarized Carbon 13 MRI: Clinical Applications and Future Directions in Oncology. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Pilot Study of Hyperpolarized 13C Metabolic Imaging in Pediatric Patients with Diffuse Intrinsic Pontine Glioma and Other CNS Cancers. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Metabolic imaging in the anesthetized rat brain using hyperpolarized [1-13C] pyruvate and [1-13C] ethyl pyruvate. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

In Vivo Metabolic Imaging of [1-13 C]Pyruvate-d3 Hyperpolarized By Reversible Exchange With Parahydrogen. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Metabolic Imaging of the Human Brain with Hyperpolarized 13C Pyruvate Demonstrates 13C Lactate Production in Brain Tumor Patients. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Imaging Glioblastoma Metabolism by Using Hyperpolarized [1-13C]Pyruvate Demonstrates Heterogeneity in Lactate Labeling: A Proof of Principle Study. [2022]